April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Transcriptional Profiling of Herpes Simplex Virus-Infected-Human Corneal Epithelium
Author Affiliations & Notes
  • Y. Terasaka
    Ophthalmology, Tottori University, Yonago, Japan
  • D. Miyazaki
    Ophthalmology, Tottori University, Yonago, Japan
  • K. Yakura
    Ophthalmology, Tottori University, Yonago, Japan
  • Y. Inoue
    Ophthalmology, Tottori University, Yonago, Japan
  • Footnotes
    Commercial Relationships  Y. Terasaka , None; D. Miyazaki, None; K. Yakura, None; Y. Inoue, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 4628. doi:
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    • Get Citation

      Y. Terasaka, D. Miyazaki, K. Yakura, Y. Inoue; Transcriptional Profiling of Herpes Simplex Virus-Infected-Human Corneal Epithelium. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4628.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : To characterize transcriptional responses of corneal epithelial cells after herpes simplex virus (HSV) infection and identify crucial signaling events via approaches utilizing network analysis.

Methods: : Immortalized human corneal epithelial cells were infected with HSV-1 strain KOS. The transcriptional responses of 30000 genes were analyzed using whole human genome chip(Agilent). Molecular networks of HSV-induced genes were constructed using GeneSpring GX7.3.1 and Ingenuity Pathway Analysis(IPA) . Representative network cascade was verified using real time-RT-PCR and ELISA.

Results: : ANOVA analysis of HSV-induced-transcriptome identified 412 genes (P<0.05, 2< or 0.5> threshold). The gene set was used to probe HSV-responsive signal transduction pathways. Pathway analysis using Kyoto Encyclopedia of Genes and Genomes identified MAP kinase signaling, cytokine-cytokine receptor interaction, focal adhesion, and carcinogenesis. Network analysis predicted IL-6 and VEGF as crucial nodes of signaling events (significance score 19).HSV-stimulated-cytokine analysis by ELISA kinetically verified their induction. Neutralization of IL-6 significantly suppressed HSV-induced-VEGF secretion.

Conclusions: : Comprehensive transcriptional analysis identified IL-6 and VEGF as presumable key modulators in HSV infected corneal epithelium. Since VEGF has been already recognized as an important player in stromal herpetic keratitis, up-regulation of VEGF in HSV corneal epithelial infection suggests very early participation of VEGF in the pathogenesis of herpetic keratitis.

Keywords: cornea: epithelium • cornea: basic science • cornea: clinical science 

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